Our previous work documented that Zn ions forms a stable bi-nuclear complex with NADPH thus inhibitng NADPH oxidation dependent reactions in liver microsomes - such as metabolism of xenobiotics by mixed function oxidases(MFO), formation of secondary carcinogens and formation of lipid peroxides. The goal of this proposal is to test that the in vitro effects of zinc as above also takes place in vivo in zinc supplemented animals. We propose that elevation of zinc in biological fluids and various liver compartments, mainly in microsomes will protect the liver against hepatotoxins and secondary hepatocarcinogens by inhibiting their metabolism by MFO. In isolated hepatocytes or in rats fed diets with various zinc content or parenterally supplemented with zinc, the liver injury induced by acute or chronic CCl4, aflatoxin B, will be studied by a complex methodology involving histology, electron microscopy, pharmacological and biochemical methods. We aim to present the evidence that supplementation of zinc protects liver against xenobiotics and secondary carcinogens. The conditions under which this occurs will be established.